LIMB-GIRDLE MUSCULAR-DYSTROPHY IN MANITOBA HUTTERITES DOES NOT MAP TOANY OF THE KNOWN LGMD LOCI

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of diso rders affecting primarily the shoulder and pelvic girdles, Autosomal d ominant and recessive forms have been identified; 8 have been mapped a nd 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolat e [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutt erite sibships with 21 patients affected with a mild autosomal recessi ve form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed, As a result, 7 asymptomatic relatives with on ly mildly elevated CK levels were assigned an unknown phenotype to pre vent their possible misclassification. Two-point linkage analysis of t he disease locus against markers linked to 7 of the known LGMD loci an d 3 other candidate genes yielded lod scores of less than or equal to 2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD. (C) 1997 Wiley-Liss, Inc.